In mammals, the natural difficulties with viviparity preclude classical, experimental embryological approaches for cell lineage studies. Genetic chimeras (mosaics, tetraparentals, allophenics) formed of two genotypically different preimplantation stage embryos, have partially overcome these difficulties and have provided useful insights into mammalian embryogenesis. These chimeras have been used to trace the origins, fates, and developmental potentialities of early embryonic cells following transfer into host blastocysts. As a result of the developmental studies performed with chimeric animals, a major limitation to their use is evident. This limitation results from the lack of a cell marker system that permits the unequivocal identification of cells of different genotypes or all cells of one genotype in histologic sections of chimeric tissues. Thus, the location and distribution of the chimeric components within tissues cannot be analyzed topographically. The full research potential of the chimeras will be realized only after such a system has been developed. Taking advantage of the naturally occurring genetic polymorphism for the electrophoretic variants of glucosephosphate isomerase (GPI) in mouse populations, we are developing immunocytochemical procedures that will reveal the distribution of the cell populations with different variants of GPI comprising mammalian chimeras. These procedures will be used to delineate fate maps of early post-implantation embryos following the production of mouse chimeras by injection and aggregation methods. Other chimeric studies will include sex differentiation in chimeras, immunologic precursor populations in the spleen, and nervous system development.